The signal transduction pathways that use mitogen-activated protein (MAP) kinases have an important role in a variety of cellular responses, including growth, stress-induced gene expression, and compensation for alterations in the environment. The Stress-Activated Protein Kinase or SAPK group of MAPKs includes the c-Jun N-terminal Kinase (JNK) and p38. SAPKs are activated strongly in response to environmental stresses such as heat and osmotic shock, UV-irradiation, exposure to genotoxic agents and pro-inflammatory cytokines. In mammalian cells, the JNK and p38 signalling pathways are involved in the response of cells to stresses such as those induced by ischaemia and reperfusion injury, they play a role in the immune response and also in the regulation of apoptosis. The p38 group of MAPK include at least four members, designated p38 or p38α, p38β, p38γ, and p38δ. Several downstream substrates of p38 have been identified, including transcription factors, protein kinases, and enzymes. Studies have indicated that activation of the p38 pathway is involved in many pathologic changes that occur during inflammatory, immunologic, and cardiovascular diseases.
There is a need in the art for improved treatment methods for various disorders such that dosage levels are adjusted based on a patient's response. The present invention addresses this need.
Literature
U.S. Pat. No. 6,579,856; U.S. Pat. No. 5,962,478; U.S. Pat. No. 6,300,349.